The structure and function of the endoplasmic reticulum of liver, kidney and testicular tissue will be assayed in toxic injury. In vivo modification will be studied following carbon tetrachloride, dibromochloropropane, ethylene dibromide and epichlorhydrene exposure and these results compared to the effects of dimethylnitrosamine, ethionine and thioacetamide. The latter represents nonhalogenated hydrocarbon liver toxins that are believed to act by different mechanisms. The endoplasmic reticulum will be isolated from control animals and subject to in vitro incubation with these same toxins. Specific attention will be directed to the mixed function oxidase activity (cytochrome P-450 and b5), phospholipid composition, and the fatty acids of the individual phospholipids. In addition the effects of induction with phenobarbital and 3-methyl-cholanthrene will be used. Reconstituted vesicles, including cytochrome P-450 and cytochrome P-450 reductase and selected phospholipid additions will be tested to activate these toxins in vitro and to determine the effect of the activation process on the fatty acid composition of the added phospholipid. Tests will be made of the hypothesis that proximate toxins have an immediate effect in the vicinity of their formation, and that this modifies the structure of the phospholipid and hence the formation of the endoplasmic reticulum.